Project Abstract /Summary Funding is requested to support the 18th Ataxia-Telangiectasia Workshop (ATW2019) to be held at the Houston Methodist Research Institute, Houston TX 77030, USA (http://www.events.houstonmethodist.org/ATW2019) from May 1-4, 2019. Approximately 45 invited speakers are planned; out of which 15-25 will be junior level researchers. The Organizing Committee will invite half the speakers based on prior contributions to the AT/ATM field with the remaining speakers being selected from attendee's abstracts: up to 150 additional abstracts can be presented as posters. We have assembled a committee of renowned workers in the A-T/ATM field to organize the meeting and select the speakers. Ataxia-telangiectasia (A-T) is a complex autosomal recessive disorder characterized by progressive cerebellar ataxia and broad neurodegenerative events, telangiectasia, immunodeficiency, genomic instability, ionizing radiation sensitivity, and a markedly increased incidence of cancer. The Ataxia telangiectasia mutated (ATM) gene mutated in A-T, encodes the ATM protein, which lies at the heart of the cellular response to/repair of DNA double strand breaks but its loss or mutation also impacts developmental processes. Our knowledge of the multiple aspects of ATM function and A-T itself is increasing as evidenced by the A-T patient clinical trials already in progress. While A-T is a rare disorder, ATM is a key DNA damage response kinase that impacts multiple cellular functions and organ systems, particularly the nervous system. Thus, it is critical that new knowledge about this disorder and ATM function is shared and communicated at the international level to inform the widest range of investigators and clinicians. The aims of this unique meeting are to: i) provide an international, interdisciplinary meeting to consider the multiple facets of ataxia telangiectasia and ATM function, ii) provide a forum to promote interactions and collaborations between clinicians, basic and translational scientists and iii) provide opportunities for junior scientists/clinicians to interact with and learn from international experts. To achieve these goals, we have assembled a program that interfaces clinical, basic and translational scientists and provides maximum opportunity for interaction between junior and senior clinicians/scientists. It is this interface between clinicians and scientists, particularly encompassing the distinct areas of relevance to A-T that represents the unique aspect of this meeting. A major feature of A-T is neuronal degeneration and recent research results have provided insight into potential ATM roles during neuronal developmental. Whilst all aspects of A-T clinical manifestations will be covered, we are specifically targeting mechanisms of neurodegeneration as a central emphasis at ATW2019.